The study of interactions between genome and exposome in the development of systemic lupus erythematosus

• Published in: Autoimmunity reviews 2019-04, Vol.18 (4), p.382-392
• Main Authors: Leffers, Henrik Christian Bidstrup, Lange, Theis, Collins, Christopher, Ulff-Møller, Constance Jensina, Jacobsen, Søren
• Format: Article
• Language: English
• Subjects: Environment; Exposome; Genetic risk; Interaction; Study design; Study power; Systemic lupus erythematosus
• ISSN: 1568-9972; 1568-9972
• DOI: 10.1016/j.autrev.2018.11.005

Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by a broad spectrum of clinical and serological manifestations. This may reflect a complex and multifactorial etiology involving several identified genetic and environmental factors, though not explaining the full risk of SLE. Established SLE risk genotypes are either very rare or with modest effect sizes and twin studies indicate that other factors besides genetics must be operative in SLE etiology. The exposome comprises the cumulative environmental influences on an individual and associated biological responses through the lifespan. It has been demonstrated that exposure to silica, smoking and exogenous hormones candidate as environmental risk factors in SLE, while alcohol consumption seems to be protective. Very few studies have investigated potential gene-environment interactions to determine if some of the unexplained SLE risk is attributable hereto. Even less have focused on interactions between specific risk genotypes and environmental exposures relevant to SLE pathogenesis. Cohort and case-control studies may provide data to suggest such biological interactions and various statistical measures of interaction can indicate the magnitude of such. However, such studies do often have very large sample-size requirements and we suggest that the rarity of SLE to some extent can be compensated by increasing the ratio of controls. This review summarizes the current body of knowledge on gene-environment interactions in SLE. We argue for the prioritization of studies that comprise the increasing details available of the genome and exposome relevant to SLE as they have the potential to disclose new aspects of SLE pathogenesis including phenotype heterogeneity. •Genetic and environmental factors cannot by far individually explain the total risk of SLE although both seem to be important.•Gene-environment interactions may add to the risk of SLE but this is only scarcely studied.•Gene-environment interaction studies are challenged by several methodological needs that can be overcome.•Identification of such interactions and their type will most likely improve our understanding of the complexity of SLE pathogenesis and phenotypes.